Aging-Specific Survival and Molecular Signatures of Glioblastoma Multiforme: Analysis of Clinical and Large-Scale Transcriptomic Data from The Cancer Genome Atlas (TCGA)

Introduction Glioblastoma multiforme (GBM) is the most common malignant brain tumor and carries a poor prognosis. Despite aggressive multimodality treatment, the median survival is approximately 18- 20 months, depending on molecular subgroups. While it’s known that older adults with GBM have a worse prognosis compared to younger patients, the precise molecular mechanism(s) and key mediator(s) of this aging-related phenomenon remain largely unknown. Methods We extracted data of 593 primary GBM patients from The Cancer Genome Atlas (TCGA) (www.cancergenome.nih.gov). The data included age at diagnosis, treatment (surgical versus non- surgical), outcome (deceased versus living), survival time, Karnofsky performance score (KPS), and gene expression profile based on RNA-Sequencing (RNA-Seq) data. For analysis, the study data was distributed into four age groups (10-44 years, 45-54 years, 55-64 years, and \u3e 65 years of age). Age-related survival and molecular signatures were identified via Kaplan-Meier survival analysis and mutational profiling. Results The median survival time (MST) of all GBM patients in this study was 12.1 months (95% confidence interval [CI], 11.1-13.1 months). The age group \u3e 65 years had the lowest MST, i.e., 7.4 months (95% CI, 5.5-9.2 months). Kaplan-Meier analysis revealed a significantly decreased survival with advancing age (log rank test, p \u3c 0.0001; Breslow test, p \u3c 0.000). The mutational profile analysis identified that PTEN, TP53, TTN, EGFR, MUC16, PIK3R1, NF1, and RYR2 mutations were found more frequently in GBM patients’ age group \u3e 65 years with shortest survival time. Conclusion Age-specific survival analysis and RNA-Seq profiling identifies a sub-set of genes more commonly mutated in older GBM patients with shorter survival time. Further characterization of the molecular signatures associated with aging in GBM patients will help identify mechanisms that contribute to GBM severity in this age group and may also lead to identification of potential therapeutic targets

Telephone Consultation for Improving Health of People Living with or at Risk of HIV: A Systematic Review

BACKGROUND: Low cost, effective interventions are needed to deal with the major global burden of HIV/AIDS. Telephone consultation offers the potential to improve health of people living with HIV/AIDS cost-effectively and to reduce the burden on affected people and health systems. The aim of this systematic review was to assess the effectiveness of telephone consultation for HIV/AIDS care. METHODS: We undertook a comprehensive search of peer-reviewed and grey literature. Two authors independently screened citations, extracted data and assessed the quality of randomized controlled trials which compared telephone interventions with control groups for HIV/AIDS care. Telephone interventions were voice calls with landlines or mobile phones. We present a narrative overview of the results as the obtained trials were highly heterogeneous in design and therefore the data could not be pooled for statistical analysis. RESULTS: The search yielded 3321 citations. Of these, nine studies involving 1162 participants met the inclusion criteria. The telephone was used for giving HIV test results (one trial) and for delivering behavioural interventions aimed at improving mental health (four trials), reducing sexual transmission risk (one trial), improving medication adherence (two trials) and smoking cessation (one trial). Limited effectiveness of the intervention was found in the trial giving HIV test results, in one trial supporting medication adherence and in one trial for smoking cessation by telephone. CONCLUSIONS: We found some evidence of the benefits of interventions delivered by telephone for the health of people living with HIV or at risk of HIV. However, only limited conclusions can be drawn as we only found nine studies for five different interventions and they mainly took place in the United States. Nevertheless, given the high penetration of low-cost mobile phones in countries with high HIV endemicity, more evidence is needed on how telephone consultation can aid in the delivery of HIV prevention, treatment and care

Physicians are a key to encouraging cessation of smoking among people living with HIV/AIDS: a cross-sectional study in the Kathmandu Valley, Nepal

BackgroundHIV care providers may be optimally positioned to promote smoking behaviour change in their patients, among whom smoking is both highly prevalent and uniquely harmful. Yet research on this front is scant, particularly in the developing country context. Hence, this study describes smoking behaviour among people living with HIV/AIDS (PLWHA) in the Kathmandu Valley of Nepal, and assesses the association between experience of physician-delivered smoking status assessment and readiness to quit among HIV-positive smokers.MethodsWe conducted a cross-sectional survey of PLWHA residing in the Kathmandu Valley, Nepal. Data from 321 adult PLWHA were analyzed using multiple logistic regression for correlates of current smoking and, among current smokers, of motivational readiness to quit based on the transtheoretical model (TTM) of behaviour change.ResultsOverall, 47% of participants were current smokers, with significantly higher rates among men (72%), ever- injecting drug users (IDUs), recent (30-day) alcohol consumers, those without any formal education, and those with higher HIV symptom burdens. Of 151 current smokers, 34% were thinking seriously of quitting within the next 6 months (contemplation or preparation stage of behaviour change). Adjusting for potential confounders, experience of physician-delivered smoking status assessment during any visit to a hospital or clinic in the past 12 months was associated with greater readiness to quit smoking (AOR = 3.34; 95% CI = 1.05,10.61).ConclusionsRoughly one-third of HIV-positive smokers residing in the Kathmandu Valley, Nepal, are at the contemplation or preparation stage of smoking behaviour change, with rates significantly higher among those whose physicians have asked about their smoking status during any clinical interaction over the past year. Systematic screening for smoking by physicians during routine HIV care may help to reduce the heavy burden of smoking and smoking-related morbidity and mortality within HIV-positive populations in Nepal and similar settings

Smoking Cessation Among Women with and at Risk for HIV: Are They Quitting?

Cigarette smoking is an important risk factor for adverse health events in HIV-infected populations. While recent US population-wide surveys report annual sustained smoking cessation rates of 3.4–8.5%, prospective data are lacking on cessation rates for HIV-infected smokers. To determine the sustained tobacco cessation rate and predictors of cessation among women with or at risk for HIV infection. Prospective cohort study. A total of 747 women (537 HIV-infected and 210 HIV-uninfected) who reported smoking at enrollment (1994–1995) in the Women’s Interagency HIV Study (WIHS) and remained in follow-up after 10 years. The participants were mostly minority (61% non-Hispanic Blacks and 22% Hispanics) and low income (68% with reported annual incomes of less than or equal to $12,000). The primary outcome was defined as greater than 12 months continuous cessation at year 10. Multivariate logistic regression was used to identify independent baseline predictors of subsequent tobacco cessation. A total of 121 (16%) women reported tobacco cessation at year 10 (annual sustained cessation rate of 1.8%, 95% CI 1.6–2.1%). Annual sustained cessation rates were 1.8% among both HIV-positive and HIV-negative women (p = 0.82). In multivariate analysis, the odds of tobacco cessation were significantly higher in women with more years of education (p trend = 0.02) and of Hispanic origin (OR = 1.87, 95% CI = 1.4–2.9) compared to Black women. Cessation was significantly lower in current or former illicit drug users (OR = 0.42 95% CI = 0.24–0.74 and OR = 0.65, 95% CI = 0.49–0.86, respectively, p trend = 0.03) and women reporting a higher number of cigarettes per day at baseline (p trend < 0.001). HIV-infected and at-risk women in this cohort have lower smoking cessation rates than the general population. Given the high prevalence of smoking, the high risk of adverse health events from smoking, and low rates of cessation, it is imperative that we increase efforts and overcome barriers to help these women quit smoking

Physical and emotional health outcomes after 12 months of public-sector antiretroviral treatment in the Free State Province of South Africa: a longitudinal study using structural equation modelling

<p>Abstract</p> <p>Background</p> <p>African and Asian cohort studies have demonstrated the clinical efficacy of antiretroviral treatment (ART) in resource-limited settings. However, reports of the long-term changes in the physical and emotional quality of life (QoL) of patients on ART in these settings are still scarce. In this study, we assessed the physical and emotional QoL after six and 12 months of ART of a sample of 268 patients enrolled in South Africa's public-sector ART programme. The study also tested the impact of the adverse effects of medication on patients' physical and emotional QoL.</p> <p>Methods</p> <p>A stratified random sample of 268 patients undergoing ART was interviewed at baseline (< 6 months ART) and follow-up (< 12 months ART). A model of the relationships between the duration of ART, the adverse effects of medication, and physical and emotional QoL (measured using EUROQOL-5D) was tested using structural equation modelling.</p> <p>Results</p> <p>The improved physical and emotional QoL shown at baseline was sustained over the 12-month study period, because treatment duration was not significantly associated with changes in the patients' QoL. Physical QoL significantly and positively influenced the patients' emotional QoL (subjective well-being [SWB]) (β = 0.33, <it>P </it>< 0.01). Longitudinal data showed that patients reported significantly fewer adverse effects at follow-up than at baseline (β = -0.38, <it>P </it>< 0.001) and that these adverse effects negatively influenced physical (β = -0.27, <it>P </it>< 0.01) and emotional QoL (β = -0.15, <it>P </it>< 0.05).</p> <p>Conclusion</p> <p>This study provides evidence that the South African public-sector ART programme is effective in delivering sustained improvement in patient well-being. However, the results should encourage clinicians and lay health workers to be vigilant regarding the adverse effects of treatment, because they can seriously affect physical and emotional QoL.</p